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Updated: Sep 19, 2026

Experimental Approaches for Biochemical Analysis of Glial Fibrillary Acidic Protein and Its Disease-associated Variants
Published on: November 28, 2025
Compound Heterozygous Mutations in FGA Cause Congenital Afibrinogenemia: A Case Report and Literature Review
Liangliang Liu1, Desheng Yuan2, Huaxing Zhao3
1Shanxi Kangbao Biological Products Co. Ltd., Changzhi, Shanxi Province, China.
Background:
Congenital afibrinogenemia is an extremely rare autosomal recessive bleeding disorder with an estimated incidence of one in one million, caused by mutations in the fibrinogen-encoding genes.
Methods:
We report a genetically confirmed case of FGA-related congenital afibrinogenemia in a 9-year-old female child. Comprehensive coagulation analysis revealed undetectable fibrinogen activity (FIB:C, < 0.2 g/L) as measured by the Clauss assay, along with significantly prolonged prothrombin time, activated partial thromboplastin time, and thrombin time.
Results:
Next-generation sequencing targeting coagulation-related genes identified compound heterozygous mutations in FGA (NM_000508): a paternal nonsense mutation c.502C>T (p.Arg168Ter) in Exon 4 and a maternal frameshift mutation c.668delT (p.Leu223ArgfsX2) in Exon 5. These pathogenic variants were further confirmed by Sanger sequencing in the proband and her parents, which demonstrated that the proband carried the two FGA variants in a compound heterozygous state, with paternal inheritance of c.502C>T and maternal inheritance of c.668delT.
Conclusion:
This case expands the genotype-phenotype correlation database for fibrinogen disorders and underscores the necessity of molecular diagnosis for congenital coagulation defects.
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